Musculocontractural Ehlers-Danlos Syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene

Abstract

To cite this version:Fransiska Malfait, Delfien Syx, Philip Vlummens, Sofie Symoens, Sheela Nampoothiri, et al.. Musculocontractural Ehlers-Danlos syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene.. Human Mutation, Wiley, 2010, 31 (11) show that both conditions form a phenotypic continuum. Our findings confirm that the EDSvariant associated with CHST14 mutations (Miyake, et al., 2010) forms a clinical spectrum, which we propose to coin as "musculo-contractural EDS" and which results from a defect in dermatan sulfate biosynthesis, perturbing collagen assembly.

A new face and new challenges for Online Mendelian Inheritance in Man (OMIM®)

“…EDS VIB had also been used to describe a different disorder now known as brittle cornea syndrome (MIM# 229200). Malfait et al [2010] reported additional patients with CHST14 mutations and confirmed the overlap of ATCS and some of the EDS VIb patients. The name for the phenotype characterized by CHST14 mutations is ''EhlersDanlos syndrome, musculocontractural type.''…”

Clinical utility gene card for: Ehlers–Danlos syndrome types I–VII and variants - update 2012

“…It is 95% for EDS type IV (COL3A1 gene), 6 EDS types VIIA and VIIB (COL1A1 and COL1A gene, respectively) and EDS type VIA (PLOD1 gene). 7 Sensitivity is not known in the recessively inherited clinical entities including Brittle Cornea syndrome 1 and 2 (ZNF469 and PRDM5 gene), 11 D4ST1-deficient EDS (CHST14 gene), 8 FKBP14-deficient EDS, 12 dermatosparactic type (ADAMTS2 gene), 9 EDS progeroid form (B4GALT7 gene) and EDS spondylocheiro dysplastic form (SLC39A13 gene). 10 …”

A response to: Loss of dermatan-4-sulfotransferase 1 (D4ST1/CHST14) function represents the first dermatan sulfate biosynthesis defect, “dermatan sulfate-deficient Adducted Thumb-Clubfoot Syndrome”. Which name is appropriate, “Adducted Thumb-Clubfoot Synd

“…Homozygous or compound heterozygous CHST14 mutations have been found in 11 patients aged 0 day to 6 years at the initial publication (from four families) with ATCS [Dündar et al, 1997[Dündar et al, , 2001[Dündar et al, , 2009Janecke et al, 2001;Sonoda and Kouno, 2000], in six patients aged 2-32 years (from six families) with EDSKT [Kosho et al, 2005Miyake et al, 2010;Yasui et al, 2003], and in three patients aged 12-22 years (from two families) with MCEDS [Malfait et al, 2010]. Lack of detailed clinical information from later childhood to adulthood in ATCS and lack of detailed clinical information from birth to early childhood in EDSKT and MCEDS have made it difficult to determine whether the three conditions would be distinct clinical entities or a single clinical entity with variable expressions and with different presentations depending on the patients' ages at diagnosis , though the latter notion was suspected to be appropriate [Janecke et al, 2011;Malfait et al, 2010].…”

“…Lack of detailed clinical information from later childhood to adulthood in ATCS and lack of detailed clinical information from birth to early childhood in EDSKT and MCEDS have made it difficult to determine whether the three conditions would be distinct clinical entities or a single clinical entity with variable expressions and with different presentations depending on the patients' ages at diagnosis , though the latter notion was suspected to be appropriate [Janecke et al, 2011;Malfait et al, 2010]. We, therefore, have just published an article in American Journal of Medical Genetics Part A, describing detailed clinical findings and courses of two additional unrelated EDSKT patients, aged 2 and 6 years, which could definitely unite the three conditions [Shimizu et al, 2011].…”

“…For patients with ATCS, the skin was assessed as normal [Dündar et al, 2009]. For those with MCEDS, most collagen bundles were found to be small sized, some of which were composed of variable diameter collagen fibrils separated by irregular interfibrillar spaces [Malfait et al, 2010]. Ultrastructural and glycobiological studies on the skin from other patients as well as those on other affected tissues such as bone, muscle, and intestine would be necessary to delineate the wide spectrum of pathophysiology.…”